2. Academic Validation
  3. African swine fever virus I267L acts as an important virulence factor by inhibiting RNA polymerase III-RIG-I-mediated innate immunity

African swine fever virus I267L acts as an important virulence factor by inhibiting RNA polymerase III-RIG-I-mediated innate immunity

  • PLoS Pathog. 2022 Jan 28;18(1):e1010270. doi: 10.1371/journal.ppat.1010270.
Yong Ran 1 2,  Dan Li 3 4,  Mei-Guang Xiong 1 2 5,  Hua-Nan Liu 3 4,  Tao Feng 3 4,  Zheng-Wang Shi 3 4,  Yu-Hui Li 1 2 5,  Huang-Ning Wu 1 2 5,  Su-Yun Wang 1 2,  Hai-Xue Zheng 3 4,  Yan-Yi Wang 1 2
Affiliations

Affiliations

  • 1 Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
  • 2 African Swine Fever Regional Laboratory of China, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
  • 3 State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
  • 4 African Swine Fever Regional Laboratory of China, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
  • 5 University of Chinese Academy of Sciences Beijing, China.
PMID: 35089988 DOI: 10.1371/journal.ppat.1010270
Abstract

ASFV is a large DNA virus that is highly pathogenic in domestic pigs. How this virus is sensed by the innate immune system as well as why it is so virulent remains enigmatic. In this study, we show that the ASFV genome contains AT-rich regions that are recognized by the DNA-directed RNA polymerase III (Pol-III), leading to viral RNA sensor RIG-I-mediated innate immune responses. We further show that ASFV protein I267L inhibits RNA Pol-III-RIG-I-mediated innate Antiviral responses. I267L interacts with the E3 ubiquitin ligase Riplet, disrupts Riplet-RIG-I interaction and impairs Riplet-mediated K63-polyubiquitination and activation of RIG-I. I267L-deficient ASFV induces higher levels of interferon-β, and displays compromised replication both in primary macrophages and pigs compared with wild-type ASFV. Furthermore, I267L-deficiency attenuates the virulence and pathogenesis of ASFV in pigs. These findings suggest that ASFV I267L is an important virulence factor by impairing innate immune responses mediated by the RNA Pol-III-RIG-I axis.

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